The overall objective of this proposal is to improve the dosimetry and treatment planning for patients receiving radioembolization treatment for unresectable hepatocellular carcinoma (HCC). Radioembolization is a novel selective internal radiation therapy that targets the delivery of radioactive 90Y glass microspheres to liver tumors, reducing side effects and limiting radiation exposure to normal liver tissues. The dose is altered by adjusting the activity of the microspheres or changing the amount of microspheres injected;the effectiveness of the therapy is highly dependent upon the number of microspheres that distribute to the tumor versus the normal parenchyma;however, current imaging modalities struggle to accurately depict in vivo microsphere biodistribution. The objective of this proposal is to develop a magnetic resonance imaging (MRI) technique to quantify the biodistribution of 90Y microspheres for improved patient dosimetry. Initial studies in our lab have demonstrated that labeling glass 90Y microspheres with Superparamagnetic Iron Oxide (SPIO) materials permits intra-hepatic MRI visualization. We propose using these SPIO-labeled microspheres and quantitative MRI measurements to permit non-invasive quantification of microsphere biodistribution. To develop and validate a new approach to quantify 90Y microsphere biodistribution, we propose the following Aims to be conducted using phantom models and the N1-S1 rodent HCC model. Aim 1: To optimize the SPIO-content of 90Y microspheres and determine the corresponding optimal set of imaging parameters for quantitative off-resonance saturation (ORS) MRI measurements. ORS is a relatively new MRI pulse sequence for detecting and quantifying SPIO particle concentrations. We need to determine the optimal off-resonance saturation frequency and associated microsphere SPIO-content that produces the strongest linear ORS signal changes proportional to corresponding changes in microsphere concentration. Hypothesis: ORS sequence parameters and microsphere SPIO-content can be optimized to produce linear concentration-dependent signal changes across a wide range of clinically relevant microsphere concentrations. Specific Aim 2: To verify that ORS MRI permits in vivo intra-hepatic quantification of SPIO-labeled 90Y microsphere biodistribution. The intra-hepatic distribution of 90Y microspheres (typically expressed as a ratio between the number of spheres delivered to the tumor and the number of spheres delivered to normal liver tissue = T/N ratio), has been strongly correlated with clinical outcomes in patients that undergo radioembolization procedures. We seek to demonstrate that the MRI methods and SPIO-labeled microspheres developed during Aim 1 can be used for in vivo T/N ratio measurements in an animal model of HCC. Hypothesis: ORS MRI of SPIO-labeled 90Y microsphere biodistribution permits accurate in vivo T/N ratio measurements in the N1-S1 rodent HCC model. PUBLIC HEALTH RELEVANCE: Radioembolization is a liver cancer treatment involving the targeting and injection of radioactive glass beads to tumors. Poor visualization of the distribution of the beads in patients makes dose selection difficult. Therefore, we are proposing an imaging method to improve the tracking of the bead biodistribution for improved dosimetry and clinical outcomes.